The broad objective of this proposal is to further define host factors which influence the initiation and progression of urinary tract infection. This objective will be approached through the following representative specific studies: (a) Determine the relationship between the perineal flora and the development of urinary tract infection and define mechanisms, both host and interbacterial, which regulate the perineal flora in humans. (b) Extend our studies of the local immune response within infected kidney and bladder to an assessment of the occurrence of cell-mediated responses and their role in antibacterial effect. In addition, further studies of humoral antibody will be performed to include a study of the influence of complement depletion on immune clearance. (c) Examine some of the non-immunological factors which may be responsible for the bladder antibacterial effect.